EP2095828A1 - Utilisation de S-adénosylméthionine (SAM) et superoxyde dismutase (SOD) pour la préparation de médicaments pour le traitement de la maladie d'Alzheimer - Google Patents
Utilisation de S-adénosylméthionine (SAM) et superoxyde dismutase (SOD) pour la préparation de médicaments pour le traitement de la maladie d'Alzheimer Download PDFInfo
- Publication number
- EP2095828A1 EP2095828A1 EP08425123A EP08425123A EP2095828A1 EP 2095828 A1 EP2095828 A1 EP 2095828A1 EP 08425123 A EP08425123 A EP 08425123A EP 08425123 A EP08425123 A EP 08425123A EP 2095828 A1 EP2095828 A1 EP 2095828A1
- Authority
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- European Patent Office
- Prior art keywords
- sam
- disease
- adenosylmethionine
- sod
- medicaments
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0089—Oxidoreductases (1.) acting on superoxide as acceptor (1.15)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
- A61K38/446—Superoxide dismutase (1.15)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to the use of S-adenosylmethionine (SAM) in combination with superoxide dismutase (SOD) for the preparation of medicaments for the treatment of Alzheimer's disease.
- SAM S-adenosylmethionine
- SOD superoxide dismutase
- AD Alzheimer's disease
- the disease also exists as a genetically transmitted form associated with mutations in some loci of chromosomes 14, 19 and 21 (typical of persons suffering from Down's syndrome).
- Early onset of the familial form of AD takes place at around 50 years old, and causes brain degeneration followed by death in 2-3 years.
- the late-onset form of the disease also gives rise to brain degeneration and death, but in a period of 10 or more years.
- Amyloid plaques also known as senile plaques, are polymers of the peptide beta-amyloid (A ⁇ ), which derives from a larger protein: beta-amyloid precursor protein (APP).
- APP is a member of the highly conserved superfamily of transmembrane glycoproteins.
- ⁇ -secretase is differentially modulated by alterations of Homocysteine cycle in neuroblastoma and glioblastoma cells. J. Alz. Dis. 11: 275-290 .
- S-adenosylmethionine can be surprisingly improved when it is administered in combination with superoxide dismutase (SOD).
- SOD superoxide dismutase
- One aspect of the invention therefore relates to products containing S-adenosylmethionine or a derivative thereof and superoxide dismutase in the form of a combined preparation for simultaneous, separate or sequential administration in the treatment of Alzheimer's disease.
- the doses can vary within a wide range in view of the very low toxicity of SAM and SOD, and will depend on a number of factors, such as the patient's weight, sex and age. However, broadly speaking, they will be between 200 and 2000 mg/day for SAM and between 50 and 1000 mg/day for SOD.
- SAM can be administered, preferably orally, either as such or in the form of a stable salt thereof such as tosylate, butanedisulphonate, disulphate tosylate, disulphate ditosylate or disulphate monotosylate.
- a stable salt thereof such as tosylate, butanedisulphonate, disulphate tosylate, disulphate ditosylate or disulphate monotosylate.
- An advantageous form of administration is Saccharomyces cerevisiae cells enriched with SAM, described in WO 2006/131382 .
- SOD obtained by fermentation from strains of Saccharomyces cerevisiae as described in WO 2006/131382 filed by the Applicant, can also be administered orally, supported on gliadin film, or using other gastroprotection techniques.
- both SAM and SOD can be administered parenterally, e.g. by intramuscular injection.
- formulations include tablets film-coated with acrylic or methacrylic polymers, gastroresistant capsules, microcapsules and the like.
- kits could be provided comprising the two drugs in separate dose forms accompanied by instructions for their sequential, simultaneous or separate use.
- mice 400 ⁇ g/day of SAM was administered orally by feeding probe needle, and the animals were sacrificed after 2 months; the animals were fed on a complete diet or a vitamin B-deprived diet, according to the trial design.
- the SAM levels were analysed by HPLC with a Varian HPLC system.
- the cells and homogenised brains were lysed in distilled water, and the macromolecules were precipitated with 1.5 M PCA.
- the standard SAM curves were calculated before and after the experimental samples.
- the cells were treated as described above, while the mice were treated for 4 days to minimise exposure to the radioactive drug.
- the cells and homogenised brains were lysed in distilled water.
- a portion of lysed brains was sonicated and centrifuged to separate the membranes and the cell organelles; another portion was treated with perchloric acid (PCA) after sonication to separate the macromolecules.
- PCA perchloric acid
- the uptake of radioactive SAM was measured by scintillation with a beta counter.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Priority Applications (27)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08425123A EP2095828A1 (fr) | 2008-02-29 | 2008-02-29 | Utilisation de S-adénosylméthionine (SAM) et superoxyde dismutase (SOD) pour la préparation de médicaments pour le traitement de la maladie d'Alzheimer |
| RU2010135467/15A RU2472513C2 (ru) | 2008-02-29 | 2009-02-25 | Применение s-аденозилметионина (sam) и супероксиддисмутазы (sod) для изготовления лекарственных средств для лечения болезни альцгеймера |
| ES09714406.7T ES2550461T3 (es) | 2008-02-29 | 2009-02-25 | Uso de S-adenosilmetionina (SAM) y superóxido dismutasa (SOD) para la preparación de medicamentos para el tratamiento de la enfermedad de Alzheimer |
| EP09714406.7A EP2249868B1 (fr) | 2008-02-29 | 2009-02-25 | Utilisation de s-adénosylméthionine (sam) et de superoxyde dismutase (sod) pour la préparation de médicaments destinés au traitement de la maladie d'alzheimer |
| BRPI0908024A BRPI0908024A2 (pt) | 2008-02-29 | 2009-02-25 | uso de s-adenosilmetionina (sam) e superóxido de dismutase (sod) para preparação de medicamentos para o tratamento de doença de alzheimer |
| CA2716893A CA2716893C (fr) | 2008-02-29 | 2009-02-25 | Utilisation de s-adenosylmethionine (sam) et de superoxyde dismutase (sod) pour la preparation de medicaments destines au traitement de la maladie d'alzheimer |
| PCT/EP2009/001323 WO2009106302A1 (fr) | 2008-02-29 | 2009-02-25 | Utilisation de s-adénosylméthionine (sam) et de superoxyde dismutase (sod) pour la préparation de médicaments destinés au traitement de la maladie d'alzheimer |
| HRP20151241TT HRP20151241T1 (hr) | 2008-02-29 | 2009-02-25 | Upotreba s-adenozilmetionina (sam) i superoksid-dismutaze (sod) za pripravu lijekova za lijeäśenje alzheimerove bolesti |
| DK09714406.7T DK2249868T3 (en) | 2008-02-29 | 2009-02-25 | Use of S-adenosylmethionine (SAM) and superoxide dismutase (SOD) for the preparation of medicaments for the treatment of Alzheimer's disease |
| CN2009801064845A CN101965197A (zh) | 2008-02-29 | 2009-02-25 | S-腺苷甲硫氨酸(sam)和超氧化物歧化酶(sod)在制备用于治疗阿尔茨海默病的药物中的用途 |
| CN201410384204.XA CN104189895B (zh) | 2008-02-29 | 2009-02-25 | S-腺苷甲硫氨酸(sam)和超氧化物歧化酶(sod)在制备用于治疗阿尔茨海默病的药物中的用途 |
| NZ587608A NZ587608A (en) | 2008-02-29 | 2009-02-25 | Use of s-adenosylmethionine (sam) and superoxide dismutase (sod) for the preparation of medicaments for the treatment of alzheimer's disease |
| AU2009218723A AU2009218723B2 (en) | 2008-02-29 | 2009-02-25 | Use of S-adenosylmethionine (SAM) and superoxide dismutase (SOD) for the preparation of medicaments for the treatment of Alzheimer's disease |
| UAA201010400A UA97440C2 (en) | 2008-02-29 | 2009-02-25 | Use of s-adenosylmethionine (sam) and superoxide dismutase (sod) for the preparation of medicaments for the treatment of alzheimer's disease |
| KR1020107018940A KR101297763B1 (ko) | 2008-02-29 | 2009-02-25 | 알츠하이머 병 치료용 의약의 제조를 위한 ｓ-아데노실메티오닌(ｓａｍ) 및 슈퍼옥시드 디스뮤타아제(ｓｏｄ)의 용도 |
| MX2010009384A MX2010009384A (es) | 2008-02-29 | 2009-02-25 | Uso de s-adenosilmetionina (sam) y superoxido dismutasa (sod) para la preparacion de medicamentos para el tratamiento de la enfermedad de alzheimer. |
| PL09714406T PL2249868T3 (pl) | 2008-02-29 | 2009-02-25 | Zastosowanie s-adenozylometioniny (sam) i dysmutazy ponadtlenkowej (sod) do wytwarzania leków do leczenia choroby alzheimera |
| SI200931313T SI2249868T1 (sl) | 2008-02-29 | 2009-02-25 | Uporaba s-adenozilmetionina (sam) in superoksid dismutaze (sod) za pripravo zdravil za zdravljenje alzheimerjeve bolezni |
| JP2010548015A JP5362747B2 (ja) | 2008-02-29 | 2009-02-25 | アルツハイマー病の治療用医薬品の調製のためのｓ−アデノシルメチオニン（ｓａｍ）およびスーパーオキシドジスムターゼ（ｓｏｄ）の使用 |
| HUE09714406A HUE028183T2 (en) | 2008-02-29 | 2009-02-25 | Use of S-adenosylmethionine (SAM) and superoxide dismutase (SOD) for the manufacture of a medicament for the treatment of Alzheimer's disease. |
| PT97144067T PT2249868E (pt) | 2008-02-29 | 2009-02-25 | Utilização de s-adenosilmetionina (sam) e superóxido dismutase (sod) para a preparação de medicamentos para o tratamento da doença de alzheimer |
| GEAP200911930A GEP20125638B (en) | 2008-02-29 | 2009-02-25 | Use of s-adenosylmethionine (sam) and superoxide dismutase (sod) for the preparation of medicaments for the treatment of alzheimer's disease |
| US12/919,515 US8778337B2 (en) | 2008-02-29 | 2009-02-25 | Use of S-adenosylmethionine (SAM) and superoxide dismutase (SOD) for the preparation of medicaments for the treatment of alzheimer's disease |
| RS20150717A RS54442B1 (sr) | 2008-02-29 | 2009-02-25 | Upotreba s-adenozilmetionina (sam) i superoksid dismutaze (sod) za pripremu lekova za lečenje alchajmerove bolesti |
| IL207807A IL207807A (en) | 2008-02-29 | 2010-08-26 | Use of s-adenosylmethionine (sam) and superoxide dismutase (sod) for the preparation of Alzheimer's drugs |
| ZA2010/06085A ZA201006085B (en) | 2008-02-29 | 2010-08-26 | Use of s-adenosylmethionine (sam) and superoxide dismutase (sod) for the preparation of medicaments for the treatment of alzheimer's disease |
| CY20151100917T CY1116782T1 (el) | 2008-02-29 | 2015-10-12 | Χρηση s-αδενοσυλμεθειονινης (sam) και υπεροξειδικης δισμουτασης (sod) για την παρασκευη φαρμακων για την αγωγη της νοσου toy alzheimer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08425123A EP2095828A1 (fr) | 2008-02-29 | 2008-02-29 | Utilisation de S-adénosylméthionine (SAM) et superoxyde dismutase (SOD) pour la préparation de médicaments pour le traitement de la maladie d'Alzheimer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2095828A1 true EP2095828A1 (fr) | 2009-09-02 |
Family
ID=39529658
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP08425123A Withdrawn EP2095828A1 (fr) | 2008-02-29 | 2008-02-29 | Utilisation de S-adénosylméthionine (SAM) et superoxyde dismutase (SOD) pour la préparation de médicaments pour le traitement de la maladie d'Alzheimer |
| EP09714406.7A Active EP2249868B1 (fr) | 2008-02-29 | 2009-02-25 | Utilisation de s-adénosylméthionine (sam) et de superoxyde dismutase (sod) pour la préparation de médicaments destinés au traitement de la maladie d'alzheimer |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP09714406.7A Active EP2249868B1 (fr) | 2008-02-29 | 2009-02-25 | Utilisation de s-adénosylméthionine (sam) et de superoxyde dismutase (sod) pour la préparation de médicaments destinés au traitement de la maladie d'alzheimer |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US8778337B2 (fr) |
| EP (2) | EP2095828A1 (fr) |
| JP (1) | JP5362747B2 (fr) |
| KR (1) | KR101297763B1 (fr) |
| CN (2) | CN104189895B (fr) |
| AU (1) | AU2009218723B2 (fr) |
| BR (1) | BRPI0908024A2 (fr) |
| CA (1) | CA2716893C (fr) |
| CY (1) | CY1116782T1 (fr) |
| DK (1) | DK2249868T3 (fr) |
| ES (1) | ES2550461T3 (fr) |
| GE (1) | GEP20125638B (fr) |
| HR (1) | HRP20151241T1 (fr) |
| HU (1) | HUE028183T2 (fr) |
| IL (1) | IL207807A (fr) |
| MX (1) | MX2010009384A (fr) |
| NZ (1) | NZ587608A (fr) |
| PL (1) | PL2249868T3 (fr) |
| PT (1) | PT2249868E (fr) |
| RS (1) | RS54442B1 (fr) |
| RU (1) | RU2472513C2 (fr) |
| SI (1) | SI2249868T1 (fr) |
| UA (1) | UA97440C2 (fr) |
| WO (1) | WO2009106302A1 (fr) |
| ZA (1) | ZA201006085B (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20150064423A (ko) * | 2013-12-03 | 2015-06-11 | 경상대학교산학협력단 | 오스모틴을 유효성분으로 함유하는 인지기능 개선용 조성물 |
| KR101689681B1 (ko) * | 2016-06-07 | 2016-12-26 | 경상대학교산학협력단 | 오스모틴을 유효성분으로 함유하는 인지기능 개선용 조성물 |
| EP4410300A4 (fr) | 2021-09-30 | 2025-10-08 | Korea Inst Oriental Medicine | Composition pour le traitement de la maladie d'alzheimer comprenant en tant que principe actif un extrait mixte de pinellia ternata breitenbach, zizyphus jujuba var. inermis rehder, glycyrrhiza uralensis fischer, panax ginseng, zingiber officinale roscoe, scutellaria baicalensis et coptis rhizome |
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| ITMI20012462A1 (it) * | 2001-11-22 | 2003-05-22 | Gnosis Srl | Processo per la preparazione di compresse comprendenti s-adenosilmetionina |
| WO2004034963A2 (fr) * | 2002-05-17 | 2004-04-29 | Eisai Co., Ltd. | Methodes et compositions utilisant des inhibiteurs de la cholinesterase |
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2008
- 2008-02-29 EP EP08425123A patent/EP2095828A1/fr not_active Withdrawn
-
2009
- 2009-02-25 BR BRPI0908024A patent/BRPI0908024A2/pt not_active Application Discontinuation
- 2009-02-25 AU AU2009218723A patent/AU2009218723B2/en active Active
- 2009-02-25 PL PL09714406T patent/PL2249868T3/pl unknown
- 2009-02-25 WO PCT/EP2009/001323 patent/WO2009106302A1/fr not_active Ceased
- 2009-02-25 JP JP2010548015A patent/JP5362747B2/ja not_active Expired - Fee Related
- 2009-02-25 KR KR1020107018940A patent/KR101297763B1/ko not_active Expired - Fee Related
- 2009-02-25 PT PT97144067T patent/PT2249868E/pt unknown
- 2009-02-25 HR HRP20151241TT patent/HRP20151241T1/hr unknown
- 2009-02-25 GE GEAP200911930A patent/GEP20125638B/en unknown
- 2009-02-25 MX MX2010009384A patent/MX2010009384A/es active IP Right Grant
- 2009-02-25 NZ NZ587608A patent/NZ587608A/xx not_active IP Right Cessation
- 2009-02-25 HU HUE09714406A patent/HUE028183T2/en unknown
- 2009-02-25 RS RS20150717A patent/RS54442B1/sr unknown
- 2009-02-25 UA UAA201010400A patent/UA97440C2/ru unknown
- 2009-02-25 CA CA2716893A patent/CA2716893C/fr active Active
- 2009-02-25 SI SI200931313T patent/SI2249868T1/sl unknown
- 2009-02-25 RU RU2010135467/15A patent/RU2472513C2/ru active
- 2009-02-25 CN CN201410384204.XA patent/CN104189895B/zh active Active
- 2009-02-25 CN CN2009801064845A patent/CN101965197A/zh active Pending
- 2009-02-25 US US12/919,515 patent/US8778337B2/en active Active
- 2009-02-25 EP EP09714406.7A patent/EP2249868B1/fr active Active
- 2009-02-25 ES ES09714406.7T patent/ES2550461T3/es active Active
- 2009-02-25 DK DK09714406.7T patent/DK2249868T3/en active
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2010
- 2010-08-26 IL IL207807A patent/IL207807A/en active IP Right Grant
- 2010-08-26 ZA ZA2010/06085A patent/ZA201006085B/en unknown
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- 2015-10-12 CY CY20151100917T patent/CY1116782T1/el unknown
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